dibekacin and Pneumonia--Staphylococcal

The efficacy and safety of once-daily high-dose arbekacin sulfate therapy for methicillin-resistant Staphylococcus aureus (MRSA) infection were evaluated, with analysis of their relationship to blood drug levels. The study was conducted in patients with pneumonia or sepsis, the cause of which was suspected to be MRSA, who were admitted to the Nagasaki University Hospital or its affiliated hospitals between January 2009 and December 2010. The initial drug dose was set at a level expected to yield the goal peak of 20 μg/ml and a trough level of less than 2 μg/ml, using the Habekacin Therapeutic Drug Monitoring analysis software. Thirteen patients were enrolled: 10 patients had pneumonia and 3 patients had sepsis. Patient mean age was 72.0 years; mean initial drug dose was 269.2 mg. Clinical efficacy at completion of treatment and bacterial eradication-reduction were achieved in 66.7% (6/9) and 62.5% (5/8) of patients, respectively. Incidence of adverse reactions was 38.5% (5/13). In analysis of efficacy in relationship to serum drug levels, the peak drug level was 22.7 ± 5.50 μg/ml, on average, and 15 μg/ml or higher in all 6 responders. Also, in patients with renal dysfunction, it seemed to be essential to ensure a certain peak drug level and to control the trough level appropriately. Although the number of patients was limited, once-daily high-dose arbekacin sulfate therapy may be highly effective, without posing any major safety problems. Further larger-scale studies are needed.

Topics: Aged; Aged, 80 and over; Anti-Infective Agents; Dibekacin; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Pneumonia, Staphylococcal; Sepsis; Staphylococcal Infections; Treatment Outcome

Arbekacin sulfate (ABK) was administered by intravenous drip to pneumonia patients infected with methicillin-resistant Staphylococcus aureus (MRSA), and the efficacy and the safety were objectively evaluated by the executive committee. The daily dose was determined in principle as 150-200 mg, two times a day, 30-90 minutes drip infusion, and the dose was to be changed at each special occasion. Combined therapy with other antibiotics was scheduled in severe cases at a decision of the physician in charge. Data of 18 cases were accumulated. The efficacy could be evaluated for 12 cases (4 cases with ABK alone, and 8 cases with combined therapy), and the safety was evaluated for 18 cases. The clinical efficacy was: excellent, 1; good, 4; fair, 5; and poor, 2. The efficacy rate was 41.7%. The bacteriological effect was: eradicated, 2 (16.7%); decreased, 2; and no change, 8. There found no side effects except 3 cases of abnormal laboratory data, two abnormal renal functions(11.1%) and one abnormal hepatic function (5.5%). In one of the renal disorders, decreased dose of ABK improved the function. In the other case, the impaired renal function lasted until death by heart failure. In the case of abnormal function, discontinuing the ABK therapy improved the hepatic function. In the 4 out of 5 cases that showed excellent or good clinical efficacy, patients recovered within relatively early days of ABK therapy. The average days for recovery was 7.8.

Topics: Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; Dibekacin; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Infusions, Intravenous; Kidney; Liver; Male; Methicillin Resistance; Middle Aged; Pneumonia, Staphylococcal; Staphylococcus aureus

Availability of arbekacin (ABK) was analyzed in the chemotherapy of 24 MRSA-infected patients with symptoms of pneumonia (12), sepsis (6) and others (6). Most patients had background diseases such as malignant tumors or cerebrovascular disorders. 47% (7/15) of them were immunologically abnormal. 17 of them had been previously treated with cephems, imipenem, minocycline or fosfomycin. The ABK therapy was performed with doses ranging 50-400 mg a day, divided into 1-3 times (mostly 100 mg x 2), and for 5-24 days. (18 patients were treated between 5 and 14 days). 14 patients (58%) received combined therapy with other antibiotics (mostly with beta-lactams, 12). The clinical efficacy rate of the ABK therapy was 62% (good, 13; fair, 4; ineffective, 4; unknown, 3). The bacteriological efficacies were: eradicated, 7 (44%); decreased, 4; no change, 5; unknown, 8. Side effects were found in 3 patients (oliguria, 2; eruption due to drug, 1) and one case resulted in serious renal disorder. Abnormal laboratory data were found in 7 cases. Above results have indicated that ABK is a useful antibiotic in chemotherapy of MRSA-infections.

Topics: Adult; Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Dibekacin; Drug Therapy, Combination; Female; Humans; Kidney; Male; Methicillin Resistance; Middle Aged; Pneumonia, Staphylococcal; Staphylococcal Infections; Staphylococcus aureus

A clinical investigation was carried out to evaluate arbekacin, an aminoglycoside, in the treatment of MRSA infections (pneumonia, septicemia, etc.) of pediatric patients. The obtained results are summarized as follows. 1.. Excluding those patients who met the present exclusion criteria and withdrawal cases from a total of 18 patients, 10 patients (3, 6, and 1 cases of septicemia, pneumonia, and urinary tract infection, respectively) were subjected to clinical evaluation. These were composed of 1, 1, 6, and 2 cases of neonate, infants, pre- and school age children, respectively. Excellent, good and fair results were obtained in 5, 2, and 3 patients, respectively; thus, the efficacy rate was 70.0%. The efficacy rate by disease was 100%, 50.0% and 100% in septicemia, pneumonia, and urinary tract infection, respectively. The bacteriological eradication were obtained in 70.0% of the total patients; by disease, these rates were 100% and 50.0% in septicemia/urinary tract infection and in pneumonia, respectively. The MIC50 as well as the MIC80 against MRSA strains isolated from 9 patients were 0.39 microgram/ml and 1.56 micrograms/ml, respectively. No adverse reactions were observed in the 15 patients, while in laboratory test values, one case each out of 12 patients examined showed gamma-GTP elevation, proteinuria, and hematuria. 2. Pharmacokinetics: The pharmacokinetics of the agent was investigated in a total of 9 patients, which included 1 neonate and 4 cases each of pre- and school age children. The Cmax, 4.85-8.83 micrograms/ml, was observed immediately after the termination of the instillation. The T1/2's were 4.96 hours, 1.24-2.54 hours, and 1.78-1.88 hours in the neonate, the pre- and the school age children, respectively; in the neonate the half-life was longer. When 1.92-2.7 mg/kg were administered to 3 each of the pre- and school age children, urinary excretion rates in the first 6-8 hours were 40.1-56.5% of the dosages administered. In all cases, the urinary concentrations were highest in the first 2 hours, after the administration, and then gradually decreased. These results suggest that arbekacin is a useful antibiotic for treating MRSA infections in the pediatric field.

Topics: Adolescent; Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Child; Child, Preschool; Dibekacin; Female; Humans; Infant; Infant, Newborn; Male; Methicillin Resistance; Pneumonia, Staphylococcal; Staphylococcal Infections; Staphylococcus aureus; Urinary Tract Infections

Arbekacin (ABK) is an aminoglycoside and widely used in Japan for treatment of patients infected with methicillin-resistant Staphylococcus aureus (MRSA). Although, ABK has concentration-dependent antibacterial activity, the peak serum concentration (C (peak)) of ABK has not yet been fully investigated as an indicator of the efficacy of ABK. The present study was conducted in patients admitted to hospitals affiliated with the ABK Dose Finding Study Group, between October 2008 and June 2011, who had pneumonia or sepsis, the cause of which was identified or suspected to be MRSA. The initial target C (peak) was set at 15-20 μg/mL and therapeutic drug monitoring was conducted. Then the relationship between serum concentration and efficacy/safety of ABK was prospectively examined to obtain sufficient clinical efficacy. In total, 89 patients from 11 clinical sites in Japan were enrolled and 29 of these patients were subjected to efficacy analysis. The mean initial dose and C (peak) were 306.9 mg/day and 16.2 μg/mL, respectively. The efficacy rate was 95 % (19/20 patients) at 5-6 mg/kg or higher, 87.5 % (7/8) for sepsis and 90.5 % (19/21) for pneumonia, and the overall efficacy rate was 89.7 % (26/29). There was no increase in the incidence of adverse events. In conclusion, we recommend the initial dose of ABK at 5-6 mg/kg or higher and the dosage regimen should be adjusted to achieve C (peak) at 10-15 μg/mL or higher in the treatment of patients with pneumonia or sepsis caused by MRSA. This strategy would surely achieve low incidence of adverse events while obtaining high clinical efficacy.

Topics: Aged; Aged, 80 and over; Anti-Infective Agents; Dibekacin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Monitoring; Female; Humans; Japan; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Pneumonia, Staphylococcal; Sepsis

We examined the peck concentration (Cmax)/minimal inhibitory concentration (MIC) and the clinical efficacy in methicillin-resistant Staphylococcus aureus (MRSA) pneumonia and Gram-positive cocci bacteremia. We evaluated arbekacin (ABK) on 22 cases of pneumonia and 10 cases of bacteremia in Aichi Medical University Hospital between August 2008 and July 2011, retrospectively. In pneumonia cases, Cmax/MIC was 16.4 +/- 2.8 in the effective group, and was 17.6 +/- 4.5 in the not effective group, the significant differences were not accepted (p = 0.8). The dosage of ABK was 4.7 +/- 1.4 mg/kg/dose in the effective group and was 4.3 +/- 0.7 mg/kg/dose in the not effective group. In bacteremia cases, Cmax/MIC was 24.2 +/- 13.9 in the effective group and 12.9 +/- 3.9 in the not effective group about clinical efficacy, and the high tendency was accepted by the effective group (p < 0.05). The dosage of ABK was 3.4 +/- 1.1 mg/kg/dose in the effective group, and 3.0 +/- 0.6 mg/kg/dose in the not effective group. In this examination, the significant difference was not observed in clinical efficacy and Cmax/MIC in the pneumonia cases. Although it was reported that clinical efficacy of ABK was given Cmax/MIC at eight or more, in this examination, all cases was eight or more at Cmax/MIC, and the clinical effect was 40.9%. On Cmax/MIC of ABK, clinical effective group was higher than not effective group in bacteremia cases, it was suggested that the administration design should make that Cmax/MIC at least about 14 or more would be necessary.

Topics: Aged; Aged, 80 and over; Anti-Infective Agents; Bacteremia; Dibekacin; Gram-Positive Cocci; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Staphylococcal

Aged or immuno-compromised patients were mostly affected, by pneumonia caused by infection of MRSA, and more than half of the cases were superinfected with glucose-nonfermentative Gram-negative rods including Pseudomonas aeruginosa. These patients were treated with a monotherapy of arbekacin (ABK) by intravenous drip administration or with a combination of ABK and imipenem/cilastatin, ceftazidime or antifungals. The clinical efficiencies were 55.6% in 11 monotherapy cases and 83.3% in combined therapy. MRSA was eradicated in 31.9% of the patients. These results are comparable with, or superior to the vancomycin therapy in the treatment of MRSA pneumonia. When MRSA is isolated from sputum of pneumonia patients, the discrimination between colonization and infection is important, but the diagnosis is very difficult in many clinical cases before the initiation of chemotherapy. The number of bacteria and the grade of inflammation should be carefully scored before starting a chemotherapy.

Topics: Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; Dibekacin; Drug Therapy, Combination; Female; Humans; Japan; Male; Methicillin Resistance; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Staphylococcal; Staphylococcus aureus; Vancomycin